This program project grant brings together molecular biologists, virologists, and experimental biologists to address the hypothesis that environmental agents (Viruses) can cause several diseases currently attributable to aging. We propose that acute or persistent virus infection can cause degenerative progressive diseases of endocrine cells, immunocompetent (lymphocytes) cells, neurons, or cells of the renal glomeruli and tubules. Such diseases, manifested in aging populations can occur through the ability of a virus to persist in specialized cells (i.e., islets of Langerhans, thyroid follicular cells, lymphocytes, endothelial cells and neurons) and turn off or abrogate their differentiated or luxury function (i.e., hormones, lympho and monokines and neurotransmitters). Such viruses may be noncytolytic and hence disease occurs by altering a cells' normal or physiologic function in the absence of the cells' destruction. Because virus induced disease can occur in the absence of tissue injury any illnesses not previously thought to be infectious in origin may be so. The second mechanism relates to the formation and action of autoantibodies leading to tissue injury. He propose that viruses can cause autoantibody (cross-reactive antibodies against self) through a process of "molecular mimicry" and/or through its effects on B or T lymphocyte subsets. In the proposed venture this group will study 1) persistent or latent infection of endocrine, immune and endothelial cells, 2) central nervous system disease associated with human retrovirus infection, 3) basic principles by which the immune system recognizes and removes foreign materials and how this is subverted by a virus to allow persistence and 4) normal and abnormal renal and vascular (endothelial) function in aging.